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| 1 | The role of the gut microbiome and its metabolites in metabolic diseases显示文摘It is well known that an unhealthy lifestyle is a major risk factor for metabolic diseases,while in recent years,accumulating evidence has demonstrated that the gut microbiome and its metabolites also play a crucial role in the onset and development of many metabolic diseases,including obesity,type 2 diabetes,nonalcoholic fatty liver disease,cardiovascular disease and so on.Numerous microorganisms dwell in the gastrointestinal tract,which is a key interface for energy acquisition and can metabolize dietary nutrients into many bioactive substances,thus acting as a link between the gut microbiome and its host.The gut microbiome is shaped by host genetics,immune responses and dietary factors.The metabolic and immune potential of the gut microbiome determines its significance in host health and diseases.Therefore,targeting the gut microbiome and relevant metabolic pathways would be effective therapeutic treatments for many metabolic diseases in the near future.This review will summarize information about the role of the gut microbiome in organism metabolism and the relationship between gut microbiome-derived metabolites and the pathogenesis of many metabolic diseases.Furthermore,recent advances in improving metabolic diseases by regulating the gut microbiome will be discussed. | Jiayu Wu Kai Wang Xuemei Wang Yanli Pang Changtao Jiang | 2021 | Protein & Cell2021，12，5： | 40 |
| 2 | Ablation of gut microbiota alleviates obesity-induced hepatic steatosis and glucose intolerance by modulating bile acid metabolism in hamsters显示文摘Since metabolic process differs between humans and mice, studies were performed in hamsters, which are generally considered to be a more appropriate animal model for studies of obesityrelated metabolic disorders. The modulation of gut microbiota, bile acids and the farnesoid X receptor(FXR) axis is correlated with obesity-induced insulin resistance and hepatic steatosis in mice. However,the interactions among the gut microbiota, bile acids and FXR in metabolic disorders remained largely unexplored in hamsters. In the current study, hamsters fed a 60% high-fat diet(HFD) were administeredvehicle or an antibiotic cocktail by gavage twice a week for four weeks. Antibiotic treatment alleviated HFD-induced glucose intolerance, hepatic steatosis and inflammation accompanied with decreased hepatic lipogenesis and elevated thermogenesis in subcutaneous white adipose tissue(sWAT). In the livers of antibiotic-treated hamsters, cytochrome P450 family 7 subfamily B member 1(CYP7 B1) in the alternative bile acid synthesis pathway was upregulated, contributing to a more hydrophilic bile acid profile with increased tauro-β-muricholic acid(TβMCA). The intestinal FXR signaling was suppressed but remained unchanged in the liver. This study is of potential translational significance in determining the role of gut microbiota-mediated bile acid metabolism in modulating diet-induced glucose intolerance and hepatic steatosis in the hamster. | Lulu Sun Yuanyuan Pang Xuemei Wang Qing Wu Huiying Liu Bo Liu George Liu Min Ye Wei Kong Changtao Jiang | 2019 | Acta Pharmaceutica Sinica B2019，9，4： | 29 |
| 3 | Disruption of adipocyte HIF-1α improves atherosclerosis through the inhibition of ceramide generation显示文摘Atherosclerosis is a chronic multifactorial cardiovascular disease.Western diets have been reported to affect atherosclerosis through regulating adipose function.In high cholesterol diet-fed ApoE^(−/−)mice,adipocyte HIF-1αdeficiency or direct inhibition of HIF-1αby the selective pharmacological HIF-1αinhibitor PX-478 alleviates high cholesterol diet-induced atherosclerosis by reducing adipose ceramide generation,which lowers cholesterol levels and reduces inflammatory responses,resulting in improved dyslipidemia and atherogenesis.Smpd3,the gene encoding neutral sphingomyelinase,is identified as a new target gene directly regulated by HIF-1αthat is involved in ceramide generation.Injection of lentivirus-SMPD3 in epididymal adipose tissue reverses the decrease in ceramides in adipocytes and eliminates the improvements on atherosclerosis in the adipocyte HIF-1α-deficient mice.Therefore,HIF-1αinhibition may constitute a novel approach to slow atherosclerotic progression. | Pengcheng Wang Guangyi Zeng Yu Yan Song-yang Zhang Yongqiang Dong Yangming Zhang Xingzhong Zhang Huiying Liu Zhipeng Zhang Changtao Jiang Yanli Pang | 2022 | Acta Pharmaceutica Sinica B2022，12，4： | 6 |
| 4 | Metabolic disorder in the progression of heart failure显示文摘Heart failure(HF) is a major clinical concern owing to its high prevalence and high mortality.Metabolomics,an effective approach to predict diagnostic biomarkers and to explore the altered metabolic pathways in pathogenesis,has been extensively applied in evaluating the course of diseases.In this study,we used this approach to analyse the abundance of metabolites,with liquid chromatograph-mass spectrometer,in plasma samples from rats with transverse aortic constriction(TAC) and patients at different stages of HF.We compared the metabolic parameters within and between TAC rats and patients.An apparent metabolic shift was observed in rats,from compensated hypertrophy stage to decompensated hypertrophy stage,and in patients with HF,from stage A to stage B and subsequently stage C.Diagnostic biomarkers were predicted by comparing the variable importance in the projection scores and fold change analysis within and between rats and patients.Enrichment pathway analysis and network analysis provided an overview of the largely disturbed metabolic pathways,and those interfered at different stages and across species were confirmed.The significantly changed metabolites and pathways revealed the underlying mechanisms of HF pathogenesis,hinted at novel potential biomarkers,and provided potential therapeutic intervention targets for HF. | Xiuxiu Zhang Huiying Liu Juan Gao Min Zhu Yupeng Wang Changtao Jiang Ming Xu | 2019 | Science China(Life Sciences)2019，62，9： | 4 |
| 5 | Single-cell RNA sequencing reveals B cell-T cell interactions in vascular adventitia of hyperhomocysteinemia-accelerated atherosclerosis显示文摘Dear Editor Cardiovascular disease(CVD)is the leading cause of death around the world(Truelsen,et al.,2015).Atherosclerosis,the dominant underlying cause of CVD,is a chronic inflam-matory disease characterized by lipid accumulation and immune cell infiltration in plaques and vessels(Weber,et al.,1950).The immune microenvironment is critical for the development of atherosclerosis.Homocysteine(Hcy)is an intermediate product of methionine metabolism,and its ele-vation in plasma(>15μmol/L),known as hyperhomocys-teinemia(HHcy),is an independent risk factor for atherosclerosis.HHcy is more common in Asia because of genetic factors and dietary habits(Huo,et al.,2015).folic acid supplement is one of the most important way to treat HHcy in clinic.Although HHcy potentiates atherosclerosis mainly through endothelial injury and inflammatory activa-tion(Luo,et al.,2016),a comprehensive understanding of the immune microenvironment and potential mechanisms in HHcy-accelerated atherosclerotic aortas(HHcy-AA)is still lacking. | Xiaolong Ma Jiacheng Deng Lulu Han Yuwei Song Yutong Miao Xing Du Guohui Dang Dongmin Yang Bitao Zhong Changtao Jiang Wei Kong Qingbo Xu Juan Feng Xian Wang | 2022 | Protein & Cell2022，13，7： | 2 |
| 6 | B cell-derived anti-beta 2 glycoprotein I antibody mediates hyperhomocysteinemia-aggravated hypertensive glomerular lesions by triggering ferroptosis显示文摘Hyperhomocysteinemia(HHcy)is a risk factor for chronic kidney diseases(CKDs)that affects about 85%CKD patients.HHcy stimulates B cells to secrete pathological antibodies,although it is unknown whether this pathway mediates kidney injury.In HHcytreated 2-kidney,1-clip(2K1C)hypertensive murine model,HHcy-activated B cells secreted anti-beta 2 glycoprotein I(β2GPI)antibodies that deposited in glomerular endothelial cells(GECs),exacerbating glomerulosclerosis and reducing renal function.Mechanistically,HHcy 2K1C mice increased phosphatidylethanolamine(PE)(18:0/20:4,18:0/22:6,16:0/20:4)in kidney tissue,as determined by lipidomics.GECs oxidative lipidomics validated the increase of oxidized phospholipids upon Hcy-activated B cells culture medium(Hcy-B CM)treatment,including PE(18:0/20:4+3[O],PE(18:0a/22:4+1[O],PE(18:0/22:4+2[O]and PE(18:0/22:4+3[O]).PE synthases ethanolamine kinase 2(etnk2)and ethanolamine-phosphate cytidylyltransferase 2(pcyt2)were increased in the kidney GECs of HHcy 2K1C mice and facilitated polyunsaturated PE synthesis to act as lipid peroxidation substrates.In HHcy 2K1C mice and Hcy-B CM-treated GECs,the oxidative environment induced by iron accumulation and the insufficient clearance of lipid peroxides caused by transferrin receptor(TFR)elevation and down-regulation of SLC7A11/glutathione peroxidase 4(GPX4)contributed to GECs ferroptosis of the kidneys.In vivo,pharmacological depletion of B cells or inhibition of ferroptosis mitigated the HHcy-aggravated hypertensive renal injury.Consequently,our findings uncovered a novel mechanism by which B cell-derived pathogenic anti-β2GPI IgG generated by HHcy exacerbated hypertensive kidney damage by inducing GECs ferroptosis.Targeting B cells or ferroptosis may be viable therapeutic strategies for ameliorating lipid peroxidative renal injury in HHcy patients with hypertensive nephropathy. | Xing Du Xiaolong Ma Ying Tan Fangyu Shao Chun Li Yang Zhao Yutong Miao Lulu Han Guohui Dang Yuwei Song Dongmin Yang Zhenling Deng Yue Wang Changtao Jiang Wei Kong Juan Feng Xian Wang | 2023 | Signal Transduction and Targeted Therapy2023，8，4： | 2 |
| 7 | Role of gut microbiota in the development of non-alcoholic fatty liver disease显示文摘Non-alcoholic fatty liver disease(NAFLD)is a chronic liver disease characterized by hepatic steatosis in the absence of other causes,such as chronic alcohol consumption,that cause secondary hepatic fat accumulation.NAFLD has become the most common liver disease worldwide over the past two decades,and the prevalence of NAFLD is 20e30%in Western countries.However,the mechanism of NAFLD re-mains unclear.The gut microbiota plays an important role in the metabolism of the host;in fact,it has been implicated in inflammatory diseases,metabolic syndrome and cardiovascular disease.Accumu-lating evidence has indicated that gut microbiota component changes are linked to human obesity,in-sulin resistance(IR),type 2 diabetes and NAFLD.Here,we provide insight into the role of gut microbiota,especially bile salt hydrolase(BSH)in modulating the bile acid pool and farnesoid X receptor(FXR),which promotes the synthesis of ceramide and contributes to the development of NAFLD. | Xuemei Wang Jialin Xia Changtao Jiang | 2019 | Liver Research2019，3，1： | 2 |
| 8 | Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease显示文摘 | Jiang Changtao Xie Cen Li Fei Zhang Limin Nichols Robert G Krausz Kristopher W Cai Jingwei Qi Yunpeng Fang Zhong-Ze Takahashi Shogo Tanaka Naoki Desai Dhimant Amin Shantu G Albert Istvan Patterson Andrew D Gonzalez Frank J | 2015 | Journal of Clinical Investigation2015，，1： | 1 |
| 9 | Adrenomedullin is a novel adipokine:Adrenomedullin in adipocytes and adipose tissues显示文摘 | Yin Li Changtao Jiang Xian Wang | 2007 | Peptides2007，28，5： | 1 |
| 10 | Crosstalk between CYP2E1 and PPARα substrates and agonists modulate adipose browning and obesity显示文摘Although the functions of metabolic enzymes and nuclear receptors in controlling physiological homeostasis have been established, their crosstalk in modulating metabolic disease has not been explored.Genetic ablation of the xenobiotic-metabolizing cytochrome P450 enzyme CYP2 E1 in mice markedly induced adipose browning and increased energy expenditure to improve obesity. CYP2 E1 deficiency activated the expression of hepatic peroxisome proliferator-activated receptor alpha(PPARa) target genes,including fibroblast growth factor(FGF) 21, that upon release from the liver, enhanced adipose browning and energy expenditure to decrease obesity. Nineteen metabolites were increased in Cyp2 e1-null mice as revealed by global untargeted metabolomics, among which four compounds, lysophosphatidylcholine and three polyunsaturated fatty acids were found to be directly metabolized by CYP2 E1 and to serve as PPARa agonists, thus explaining how CYP2 E1 deficiency causes hepatic PPARa activation through increasing cellular levels of endogenous PPARa agonists. Translationally, a CYP2 E1 inhibitor was found to activate the PPARa-FGF21-beige adipose axis and decrease obesity in wild-type mice, but not in liver-specific Pparanull mice. The present results establish a metabolic crosstalk between PPARa and CYP2 E1 that supports the potential for a novel anti-obesity strategy of activating adipose tissue browning by targeting the CYP2 E1 to modulate endogenous metabolites beyond its canonical role in xenobiotic-metabolism. | Youbo Zhang Tingting Yan Tianxia Wang Xiaoyan Liu Keisuke Hamada Dongxue Sun Yizheng Sun Yanfang Yang Jing Wang Shogo Takahashi Qiong Wang Kristopher W.Krausz Changtao Jiang Cen Xie Xiuwei Yang Frank J.Gonzalez | 2022 | Acta Pharmaceutica Sinica B2022，12，5： | 1 |
| 11 | Activation of Pancreatic Acinar FXR Protects against Pancreatitis via Osginl-Mediated Restoration of Efficient Autophagy显示文摘Pancreatitis is the leading cause of hospitalization in gastroenterology,and no medications are available for treating this disease in current clinical practice.FxR plays an anti-inflammatory role in diverse inflammatory diseases,while its function in pancreatitis remains unknown.In this study,we initially observed a marked increase of nuclear FXR in pancreatic tissues of human patients ithpancratis eleting theFXRinpancreati acinar cels FXRicnara/a)ledto moreseverepancreatitis in mousemodels of caerulein-induced acute and chronic pancreatitis,while the FXR agonist GW4064 significantly attenuated pancreatitis in caerulein or arginine-induced acute pancreatitis and caerulein-induced chronic pancreatitis.FXR deletion impaired the viability and stress responses of pancreatic exocrine organoids(PEOs)in vitro.Utilizing RNA-seq and ChIP-seq of PEOs,we identified Osginl as a direct target of FxR in the exocrine pancreas,which was also increasingly expressed in human pancreatitis tissues compared to normal pancreatic tissues.Pancreatic knockdown of Osgin1 by AAV-pan abolished the therapeutic effects of FXR activation on pancreatitis,whereas pancreatic overexpression of Osginl effectively alleviated caerulein-induced pancreatitis.Mechanistically,we found that the FXR-OSGINl axis stimulated autophagic flux in the pancreatic tissues and cell lines,which was considered as the intrinsic mechanisms through which FXR-OSGINI protecting against pancreatitis.Our results highlight the protective role of the FXR-OSGIN1 axis in pancreatitis and provided a new target for the treatment of this disease. | Yufan Zheng Wenrui Sun Zhengyang Wang Jiaying Liu Cong Shan Chenxi He Borui Li Xiao Hu Wenjia Zhu Liyan Liu Fei Lan Changtao Jiang Chao Zhao Xiaobo Li Ning Sun | 2023 | Research2023，，1： | 0 |
| 12 | Advances in regulation and function of stearoyl-CoA desaturase 1 in cancer,from bench to bed显示文摘Stearoyl-CoA desaturase 1(SCD1)converts saturated fatty acids to monounsaturated fatty acids.The expression of SCD1 is increased in many cancers,and the altered expression contributes to the proliferation,invasion,stemness and chemoresistance of cancer cells.Recently,more evidence has been reported to further support the important role of SCD1 in cancer,and the regulation mechanism of SCD1 has also been focused.Multiple factors are involved in the regulation of SCD1,including metabolism,diet,tumor microenvironment,transcription factors,non-coding RNAs,and epigenetics modification.Moreover,SCD1 is found to be involved in regulating ferroptosis resistance.Based on these findings,SCD1 has been considered as a potential target for cancer treatment.However,the resistance of SCD1 inhibition may occur in certain tumors due to tumor heterogeneity and metabolic plasticity.This review summarizes recent advances in the regulation and function of SCD1 in tumors and discusses the potential clinical application of targeting SCD1 for cancer treatment. | Zhengyang Guo Xiao Huo Xianlong Li Changtao Jiang Lixiang Xue | 2023 | Science China(Life Sciences)2023，66，12： | 0 |
| 13 | Gut microbiota,immunity,and bile acid metabolism:decoding metabolic disease interactions显示文摘In recent decades,the global prevalence of metabolic syndrome has surged,posing a significant public health challenge.Metabolic disorders,encompassing diabetes,obesity,nonalcoholic fatty liver disease,and polycystic ovarian syndrome,have been linked to alterations in the gut microbiota.Nonetheless,the connection between gut microbiota and host metabolic diseases warrants further investigation.In this review,we delve into the associations between various metabolic disorders and the gut microbiota,focusing on immune responses and bile acid(BA)metabolism.Notably,T helper cells,innate lymphoid cells,macrophages,and dendritic cells have been shown to modulate host metabolism through interactions with intestinal microorganisms and the release of cytokines.Furthermore,secondary BA metabolites,derived from the microbiota,are involved in the pathogenesis of metabolic diseases via the farnesoid X receptor and Takeda G protein-coupled receptor 5.By covering both aspects of this immune system-microorganism axis,we present a comprehensive overview of the roles played by the gut microbiota,microbiota-derived BA metabolites,and immune responses in metabolic diseases,as well as the interplay between these systems. | Qixiang Zhao Jiayu Wu Yong Ding Yanli Pang Changtao Jiang | 2023 | Life Metabolism2023，2，6： | 0 |
| 14 | Microbial transformations of bile acids and their receptors in the regulation of metabolic dysfunction-associated steatotic liver disease显示文摘Bile acids(BAs)play important roles in the digestion of dietary fats and molecular signal transduction,and modulation of the BA composition usually affects the progression of metabolic diseases.While the liver produces primary BAs,the gut microbiota modifies these products into various forms that greatly increase their diversity and biological functions.Mechanistically,BAs can regulate their own metabolism and transport as well as other key aspects of metabolic processes via dedicated BA receptors.Disruption of BA transport and homeostasis leads to the progression of liver diseases,including metabolic dysfunction-associated steatotic liver disease(MASLD)and hepatocellular carcinoma(HCC).Here,we summarize the microbial transformations of BAs and their downstream signaling in the development of metabolic diseases and present new insights into novel therapeutic strategies targeting BA pathways that may contribute to these diseases. | Yuhua Gao Jun Lin Chuan Ye Siqi Guo Changtao Jiang | 2023 | Liver Research2023，7，3： | 0 |
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